The long range goal of our program is to correct the age-associated changes in immune function that contribute to human disease. Toward this end, this program brings together three inter-related projects to study the mechanisms underlying the spontaneous appearance of stable B and/or T cell clonal expansions with age. First of all, the role of age-associated decreased diversity of the lymphoid repertoire to the appearance of clonal lymphocyte expansions will be studied. IN addition, the role of antigen stimulation and/or impaired clonal homeostasis in the persistence of clonal lymphocyte populations will be examined. A key question is to determine whether the presence of clonal lymphocytes contribute to the impaired immune function seen in old mice. That is, do to age-associated lymphoid clonal expansions, by decreasing the diversity of the lymphoid repertoire or by the production of specific cytokines, contribute to immune senescence. The function of spontaneously-appearing T cell clones in old mice will be compared to that of transgenic anti-influenza T cell clones which are present from birth. The influence of anti-influenza T cell clones on the immune system of young and old mice as well as the function of the anti- influenza TCR T cell clone in young and old mice will be studied.